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- Mosharraf, MitraUppsala universitet,Institutionen för farmaci (author)
The effects of solid state properties on solubility and "in vitro" dissolution behaviour of suspended sparingly soluble drugs
- BookEnglish1999
Publisher, publication year, extent ...
- Uppsala :Acta Universitatis Upsaliensis,1999
- 81 s.
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:uu-977
- ISBN:9155444741
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-977URI
Supplementary language notes
- Language:English
- Summary in:English
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- SwePubSwePub
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Series
- Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy,0282-7484 ;206
Notes
- The solubility and dissolution behaviour of hydrophobic and hydrophilic sparingly soluble drugs is discussed in this thesis. The roles of varying particle dimensions, disordered (amorphous) solid structures and the coexistence of amorphous and crystalline phases, especially on the surfaces of particles with a crystalline core, are evaluated in this context.A simplified solubility model, based on the application of a wide range of dispersion concentrations during the characterisation of saturation concentrations (apparent solubilities), is proposed in order to qualitatively describe the relationship between established apparent solubilities and different combinations of solid structures.Several solubility plateaux were found, for a range of practically insoluble materials, in a plot of the established saturation concentration versus dispersion concentration. The lowest and highest solubility plateaux correspond to the solubilities of the totally ordered and totally disordered standards (one-component model). An intermediate plateau serves as an indication of the existence of a totally semiordered structure (one-component model) Such a structure was proposed for one type of quenched griseofulvin, where the prepared particles were described as glassy and homogeneously semiordered.However, the saturation concentrations of two-component materials, containing a partly or totally disordered solid surface on a crystalline core (obtained by milling or mixing) were significantly dependent on the dispersion concentration, only reaching the plateau saturation concentrations of the totally disordered or semiordered one-component standards at very high dispersion concentrations. The dissolution rate profiles of solids with a peripheral disordered layer, in contrast to those of totally crystalline solids, were biphasic, which indicates that the solid state structure and solid state reactivity of the inter-phase will affect the dissolution rate of a drug. It was also shown that the effects of particle dimensions on the intrinsic dissolution rate of a drug are not limited to the interfacial surface area. It is suggested that the thickness of the diffusion layer controlling the dissolution rate is a function of both the size and shape of the particle (i.e. it decreases for small, isodiametric particles), thus linking dissolution and particle hydrodynamics.Alterations to a recently developed method for determining the solubility of practically insoluble drugs, using the Coulter counter technique, are also presented. This method now allows detection of the solubility of drugs at concentrations as low as 0.1 ppm.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmaceutical Sciences hsv//eng
- Pharmacy
- FARMACI
- PHARMACY
- FARMACI
- galenisk farmaci
- Pharmaceutics
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- Uppsala universitetInstitutionen för farmaci (creator_code:org_t)
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